Caffeine: A vitamin-like nutrient, or adaptogen. Questions about tea and coffee, cancer and other degenerative diseases, and the hormones.
A R T I C L E

Caffeine: A vitamin-like nutrient, or adaptogen

Questions about tea and coffee, cancer and other degenerative diseases, and the hormones.

There
is a popular health-culture that circulates mistaken ideas about nutrition,
and coffee drinking has been a perennial target of this culture.
It is commonly said that coffee is a drug, not a food, and that its
drug action is harmful, and that this harm is not compensated by any
nutritional benefit. Most physicians subscribe to most of these
“common sense” ideas about coffee, and form an authoritative barrier
against the assimilation of scientific information about coffee.

I
think it would be good to reconsider coffee’s place in the diet and
in health care.

Coffee
drinkers have a lower incidence of thyroid disease, including cancer,
thannon-drinkers.

Caffeine
protects the liver from alcohol and acetaminophen (Tylenol) and other
toxins, and coffee drinkers are less likely than people who don’t
use coffee to have elevated serum enzymes and other indications of liver
damage.

One
definition of a vitamin is that it is an organic chemical found in foods,
the lack of which causes a specific disease,
or group of diseases. A variety of substances that have been proposed
to be vitamins haven’t been recognized as being essential, and some
substances that aren’t essential are sometimes called vitamins.
Sometimes these issues haven’t had enough scientific investigation,
but often nonscientific forces regulate nutritional ideas.

The
definition of “a disease” isn’t as clear as text-book writers
have implied, and “causality” in biology is always more complex
than we like to believe.

Nutrition
is one of the most important sciences, and should certainly be as prestigious
and well financed as astrophysics and nuclear physics, but while people
say “it doesn’t take a brain surgeon to figure that out,” no one
says “it doesn’t take a nutritionist to understand that.”
Partly, that’s because medicine treated scientific nutrition as an
illegitimate step-child, and refused throughout the 20th century to
recognize that it is a central part of scientific health care.
In the 1970s, physicians and dietitians were still ridiculing the idea
that vitamin E could prevent or cure diseases of the circulatory system,
and babies as well as older people were given “total intravenous nutrition”
which lacked nutrients that are essential to life, growth, immunity,
and healing. Medicine and science are powerfully institutionalized,
but no institution or profession has existed for the purpose of encouraging
people to act reasonably.

In
this environment, most people have felt that subtleties of definition,
logic and evidence weren’t important for nutrition, and a great amount
of energy has gone into deciding whether there were “four food groups”
or “seven food groups” or a “nutritional pyramid.” The
motives behind governmental and quasi-governmental nutrition policies
usually represent something besides a simple scientific concern for
good health, as when health care institutions say that Mexican babies
should begin eating beans when they reach the age of six months, or
that non-whites don’t need milk after they are weaned. In a
culture that discourages prolonged breast feeding, the effects of these
doctrines can be serious.

After
a century of scientific nutrition, public nutritional policies are doing
approximately as much harm as good, and they are getting worse faster
than they are getting better..

In
this culture, what we desperately need is a recognition of the complexity
of life, and of the political-ecological situation we find ourselves
in. Any thinking which isn’t “system thinking” should be treated
with caution, and most contemporary thinking about health neglects to
consider relevant parts of the problem-system. “Official”
recommendations about salt, cholesterol, iron, unsaturated and saturated
fats, and soybeans have generally been inappropriate, unscientific,
and strongly motivated by business interests rather than by biological
knowledge.

Definitions
have rarely distinguished clearly between nutrients and drugs, and new
commercial motives are helping to further blur the distinctions.

Essential
nutrients, defensive (detoxifying,
antistress) nutrients, hormone-modulating nutrients, self-actualization
nutrients, growth regulating nutrients, structure modifiers, life extension
agents, transgenerationally active (imprinting)nutrients--the
line between nutrients and biological modifiers often depends on the
situation. Vitamins D and A clearly have hormone-like properties, and
vitamin E’s effects, and those of many terpenoids and steroids and
bioflavonoids found in foods, include hormone-like actions as well as
antioxidant and pro-oxidant functions. The concept of “adaptogen”
can include things that act like both drugs and nutrients.

Some
studies have suggested that trace amounts of nutrients could be passed
on for a few generations, but the evidence now indicates that these
transgenerational effects are caused by phenomena such as “imprinting.”
But the hereditary effects of nutrients are so complex that their recognition
would force nutrition to be recognized as one of the most complex sciences,
interwoven with the complexities of growth and development.

The
idea that poor nutrition stunts growth has led to the idea that good
nutrition can be defined in terms of the rate of growth and the size
ultimately reached. In medicine, it is common to refer to an obese
specimen as “well nourished,” as if quantity of food and quantity
of tissue were necessarily good things. But poisons can stimulate
growth (“hormesis”),
and food restriction can extend longevity. We still have to
determine basic things such as the optimal rate of growth, and the optimal
size.

Nutrition
textbooks flatly describe caffeine as a drug, not a nutrient, as if
it were obvious that nutrients can’t be drugs. Any of the essential
nutrients, if used in isolation, can be used as a drug, for a specific
effect on the organism that it wouldn’t normally have when eaten as
a component of ordinary food. And natural foods contain thousands
of chemicals, other than the essential nutrients. Many of these
are called nonessential nutrients, but their importance is being recognized
increasingly. The truth is that we aren’t sure what they “aren’t
essential” for. Until we have more definite knowledge about
the organism I don’t think we should categorize things so absolutely
as drugs or nutrients.

The
bad effects ascribed to coffee usually involve administering large doses
in a short period of time. While caffeine is commonly said to
raise blood pressure, this effect is slight, and may not occur during
the normal use of coffee. Experimenters typically ignore essential
factors. Drinking plain water can cause an extreme rise in blood
pressure, especially in old people, and eating a meal (containing carbohydrate)
lowers blood pressure. The increased metabolic rate caffeine produces
increases the cellular consumption of glucose, so experiments that study
the effects of coffee taken on an empty stomach are measuring the effects
of increased temperature and metabolic rate, combined with increased
adrenaline (resulting from the decrease of glucose), and so confuse
the issue of caffeine’s intrinsic effects.

In
one study (Krasil’nikov, 1975), the drugs were introduced directly
into the carotid artery to study the effects on the blood vessels in
the brain. Caffeine increased the blood volume in the brain, while
decreasing the resistance of the vessels, and this effect is what would
be expected from its stimulation of brain metabolism and the consequent
increase in carbon dioxide, which dilates blood vessels.

In
the whole body, increased carbon dioxide also decreases vascular resistance,
and this allows circulation to increase, while the heart’s work is
decreased, relative to the amount of blood pumped. But when the
whole body’s metabolism is increased, adequate nutrition is crucial.

In
animal experiments that have been used to argue that pregnant women
shouldn’t drink coffee, large doses of caffeine given to pregnant
animals retarded the growth of the fetuses. But simply giving
more sucrose prevented the growth retardation. Since caffeine
tends to correct some of the metabolic problems that could interfere
with pregnancy, it is possible that rationally constructed experiments
could show benefits to the fetus from the mother’s use of coffee,
for example by lowering bilirubin and serotonin, preventing hypoglycemia,
increasing uterine perfusion and progesterone synthesis, synergizing
with thyroid and cortisol to promote lung maturation, and providing
additional nutrients.

One
of the most popular misconceptions about caffeine is that it causes
fibrocystic breast disease. Several groups demonstrated pretty
clearly that it doesn’t, but there was no reason that they should
have had to bother, except for an amazingly incompetent, but highly
publicized, series of articles--classics of their kind--by J. P. Minton,
of Ohio State University. Minton neglected to notice that the
healthy breast contains a high percentage of fat, and that the inflamed
and diseased breast has an increased proportion of glandular material
Fat cells have a low level of cyclic AMP, a regulatory substance that
is associated with normal cellular differentiation and function, and
is involved in mediating caffeine’s ability to inhibit cancer cell
multiplication. Minton
argued that cAMP increases progressively with the degree of breast disease,
up to cancer, and that cAMP is increased by caffeine. A variety
of substances other than caffeine that inhibit the growth of cancer
cells (as well as normal breast cells) act by increasing the
amount of cyclic AMP, while estrogen lowers the amount of cAMP and increases
cell growth. Minton’s argument should have been to use more
caffeine, in proportion to the degree of breast disease, if he were
arguing logically from his evidence. Caffeine’s effect on the
breast resembles that of progesterone, opposing estrogen’s effects.

Many
studies over the last 30 years have shown caffeine to be highly protective
against all kinds of carcinogenesis, including estrogen’s carcinogenic
effects on the breast. Caffeine is now being used along with some
of the standard cancer treatments, to improve their effects or to reduce
their side effects. There are substances in the coffee berry besides
caffeine that protect against mutations and cancer, and that have shown
strong therapeutic effects against cancer. Although many plant
substances are protective against mutations and cancer, I don’t know
of any that is as free of side effects as coffee.

To
talk about caffeine, it’s necessary to talk about uric acid.
Uric acid, synthesized in the body, is both a stimulant and a very important
antioxidant, and its structure is very similar to that of caffeine.
A deficiency of uric acid is a serious problem. Caffeine and uric
acid are in the group of chemicals called purines.

Purines
(along with pyrimidines) are components of the nucleic acids, DNA and
RNA, but they have many other functions. In general, substances
related to purines are stimulants, and substances related to pyrimidines
are sedatives.

When
the basic purine structure is oxidized, it becomes in turn hypoxanthine,
xanthine, and uric acid, by the addition of oxygen atoms. When
methyl groups (CH3) are added to nitrogens in the purine
ring, the molecule becomes less water soluble. Xanthine (an intermediate
in purine metabolism) has two oxygen atoms, and when three methyl groups
are added, it becomes trimethyl xanthine, or caffeine. With two
methyl groups, it is theophylline,
which is named for its presence in tea. We have enzyme systems
which can add and subtract methyl groups; for example, when babies
are given theophylline, they can convert it into caffeine.

We
have enzymes that can modify all of the methyl groups and oxygen atoms
of caffeine and the other purine derivatives. Caffeine is usually
excreted in a modified form, for example as a methylated uric acid.

One
of the ways in which uric acid functions as an “antioxidant” is
by modifying the activity of the enzyme xanthine oxidase, which in stress
can become a dangerous source of free radicals. Caffeine also
restrains this enzyme. There are several other ways in which uric
acid and caffeine (and a variety of intermediate xanthines) protect
against oxidative damage. Coffee drinkers, for example, have been
found to have lower levels of cadmium in their kidneys than people who
don’t use coffee, and coffee is known to inhibit the absorption of
iron by the intestine, helping to prevent iron overload.

Toxins
and stressors often kill cells, for example in the brain, liver, and
immune system, by causing the cells to expend energy faster than it
can be replaced. There is an enzyme system that repairs genetic
damage, called “PARP.” The activation of this enzyme is a
major energy drain, and substances that inhibit it can prevent the death
of the cell. Niacin and caffeine can inhibit this enzyme sufficiently
to prevent this characteristic kind of cell death, without preventing
the normal cellular turnover; that is, they don’t produce tumors
by preventing the death of cells that aren’t needed.

The
purines are important in a great variety of regulatory processes, and
caffeine fits into this complex system in other ways that are often
protective against stress. For example, it has been proposed that
tea can protect against circulatory disease by preventing abnormal clotting,
and the mechanism seems to be that caffeine (or theophylline) tends
to restrain stress-induced platelet aggregaton.

When
platelets clump, they release various factors that contribute to the
development of a clot. Serotonin is one of these, and is released
by other kinds of cell, including mast cells and basophils and nerve
cells. Serotonin produces vascular spasms and increased blood
pressure, blood vessel leakiness and inflammation, and the release of
many other stress mediators. Caffeine, besides inhibiting the
platelet aggregation, also tends to inhibit the release of serotonin,
or to promote its uptake and binding.

J.
W. Davis, et al., 1996, found that high uric acid levels seem to protect
against the development of Parkinson’s disease. They ascribed
this effect to uric acid’s antioxidant function. Coffee drinking,
which lowers uric acid levels, nevertheless appeared to be much
more strongly protective against Parkinson’s disease than uric acid.

Possibly
more important than coffee’s ability to protect the health is the
way it does it. The studies that have tried to gather evidence
to show that coffee is harmful, and found the opposite, have provided
insight into several diseases. For example, coffee’s effects
on serotonin are very similar to carbon dioxide’s, and the thyroid
hormone’s. Noticing that coffee drinking is associated with
a low incidence of Parkinson’s disease could focus attention on the
ways that thyroid and carbon dioxide and serotonin, estrogen, mast cells,
histamine and blood clotting interact to produce nerve cell death.

Thinking
about how caffeine can be beneficial across such a broad spectrum of
problems can give us a perspective on the similarities of their underlying
physiology and biochemistry, expanding the implications of stress, biological
energy, and adaptability.

The
observation that coffee drinkers have a low incidence of suicide, for
example, might be physiologically related to the large increase in suicide
rate among people who use the newer antidepressants called “serotonin
reuptake inhibitors.” Serotonin excess causes several of the
features of depression, such as learned helplessness and reduced metabolic
rate, while coffee stimulates the uptake (inactivation or storage)
of serotonin, increases metabolic energy, and tends to improve mood.
In animal studies, it reverses the state of helplessness or despair,
often more effectively than so-called antidepressants.

The
research on caffeine’s effects on blood pressure, and on the use of
fuel by the more actively metabolizing cells, hasn’t clarified its
effects on respiration and nutrition, but some of these experiments
confirm things that coffee drinkers usually learn for themselves.

Often,
a woman who thinks that she has symptoms of hypoglycemia says that drinking
even the smallest amount of coffee makes her anxious and shaky.
Sometimes, I have suggested that they try drinking about two ounces
of coffee with cream or milk along with a meal. It’s common
for them to find that this reduces their symptoms of hypoglycemia, and
allows them to be symptom-free between meals. Although we don’t
know exactly why caffeine improves an athlete’s endurance, I think
the same processes are involved when coffee increases a person’s “endurance”
in ordinary activities.

Caffeine
has remarkable parallels to thyroid and progesterone, and the use of
coffee or tea can help to maintain their production, or compensate for
their deficiency. Women spontaneously drink more coffee premenstrually,
and since caffeine is known to increase the concentration of progesterone
in the blood and in the brain, this is obviously a spontaneous and rational
form of self-medication, though medical editors like to see things causally
reversed, and blame the coffee drinking for the symptoms it is actually
alleviating. Some women have noticed that the effect of a progesterone
supplement is stronger when they take it with coffee. This is
similar to the synergy between thyroid and progesterone, which is probably
involved, since caffeine tends to locally activate thyroid secretion
by a variety of mechanisms, increasing cyclic AMP and decreasing serotonin
in thyroid cells, for example,
and also by lowering the systemic stress mediators.

Medical
editors like to publish articles that reinforce important prejudices,
even if, scientifically, they are trash. The momentum of a bad
idea can probably be measured by the tons of glossy paper that have
gone into its development. Just for the sake of the environment,
it would be nice if editors would try to think in terms of evidence
and biological mechanisms, rather than stereotypes.

REFERENCES

Fiziol
Zh SSSR Im I M Sechenova 1975 Oct;61(10):1531-8. [Changes in the
resistance and capacity of the cerebral vascular bed under the influence
of vasoactive substances]. [Article in Russian] Krasil'nikov, V.G.
Effects of intracarotid injections of vasoactive agents on cerebrovascular
resistance (CVR) and cerebral blood volume (CBV) were studied in hemodynamically
isolated brain of cats. Perfusion pressure shifts at a constant blood
volume perfusion reflected CVR changes, and changes of venous outflow
- CBV alterations. Administration of adrenaline, serotonin, and angiotensine
was followed mainly by an increase of CVR and a decrease of CBV.
The CVR could
be reduced by isopropilnoradrenaline,
acetylcholine, histamine, and caffeine.CBV was decreased after
isopropilnoradrenaline, acetycholine, histamine injections and increased
by caffeine. The possible role of the active changes of cerebral
capacitance vessels in the transcapillary fluid exchange is discussed.
Capacitance vessels active responses are supposed to entail wrong results
when using certain techniques for measurement of cerebral blood flow
and metabolism.

Proc
Soc Exp Biol Med 1999 Apr;220(4):244-8. The prevention of lung cancer
induced by a tobacco-specific carcinogen in rodents by green and black
Tea. Chung FL “The oxidation products found in black tea, thearubigins
and theaflavins, also possess antioxidant activity, suggesting that
black tea may also inhibit NNK-induced lung tumorigenesis. Indeed, bioassays
in A/J mice have shown that black tea given as drinking water retarded
the development of lung cancer caused by NNK.” “We conducted a 2-year
lifetime bioassay in F344 rats to determine whether black tea and
caffeine are protective against lung
tumorigenesis induced by NNK. Our studies in both mice and rats have
generated important new data that support green and black tea and
caffeine as potential preventive agents against lung cancer, suggesting
that a closer examination of the roles of tea and caffeine on lung cancer
in smokers may be warranted.”

Pharmacol
Biochem Behav 2000 May;66(1):39-45. Caffeine-induced increases in
the brain and plasma concentrations of
neuroactive steroids in the rat. Concas A, Porcu P, Sogliano
C, Serra M, Purdy RH, Biggio G. “A single intraperitoneal injection
of caffeine induced dose- and time-dependent increases in the concentrations
of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one
(allopregnanolone) in the cerebral cortex.” “Caffeine also
increased the plasma concentrations of
pregnenolone and progesterone with a dose-response relation similar
to that observed in the brain . . .”
“Moreover, the brain and plasma concentrations of pregnenolone,
progesterone, and allopregnanolone were not affected by caffeine in
adrenalectomized-orchiectomized rats.”

Cancer
Res 1998 Sep 15;58(18):4096-101. Inhibition oflung
carcinogenesis by black tea in Fischer rats treated with a tobacco-specific
carcinogen: caffeine as an important constituent. Chung FL, Wang
M, Rivenson A, Iatropoulos MJ, Reinhardt JC, Pittman B, Ho CT, Amin
SG. “The NNK-treated group, given 2% black tea, showed a significant
reduction of the total lung tumor (adenomas,
adenocarcinomas, and adenosquamous carcinomas) incidence from 47% to
19%, whereas the group given 1% and 0.5% black tea showed no change.
The 2% tea also reduced liver tumor incidence induced by NNK from
34% in the group given only deionized water to 12%.” “The most
unexpected finding was the remarkable reduction of the lung tumor incidence,
from 47% to 10%, in the group treated with 680
ppm caffeine, a concentration equivalent to that found in the 2% tea.
This incidence is comparable to background levels seen in the control
group. This study demonstrated for the first time in a 2-year lifetime
bioassay that black tea protects against lung tumorigenesis in F344
rats, and this effect appears to be attributed, to a significant
extent, to caffeine as an active ingredient of tea.”

Cancer
1985 Oct 15;56(8):1977-81. The inhibitory effect of caffeine on hormone-induced
rat breast cancer. Petrek JA, Sandberg WA, Cole MN, Silberman MS,
Collins DC. “The current investigation examines the effect of two
caffeine doses in ACI rats with and without diethylstilbestrol (DES).
Without DES, cancer did not develop in any of the rats receiving either
of the two caffeine dosages. With DES, increasing caffeine dosage lengthened
the time to first cancer, decreased the number of rats that developed
cancers, and decreased the number of cancers overall.” “In conclusion,
chronic caffeine ingestion inhibits rat breast cancer, neither by interfering
with the high prolactin levels--a necessary step in murine tumor development--nor
by causing hypocaloric intake.”

Nutr Cancer 1998;30(1):21-4. Association of coffee, green tea, and
caffeine intakes with serum concentrations of
estradiol and sex hormone-binding globulin in
premenopausal Japanese women. Nagata C, Kabuto M, Shimizu H. “Although
the effect of caffeine cannot be distinguished from effects of coffee
and green tea, consumption of caffeine-containing beverages appeared
to favorably alter hormone levels associated with the risk of developing
breast cancer.”

J
Environ Pathol Toxicol Oncol 1994;13(2):81-8. Enhancement by caffeine
of mammary gland lobulo-alveolar development in mice: a function of
increased corticosterone. Welsch CW, VanderPloeg LC. Previously
we have reported that the stimulatory effect of caffeine on
lobulo-alveolar development in the mammary glands of female Balb/c
mice is not due to a direct action of the drug on the mammary gland
but appears to be due to a caffeine-induced alteration of a yet to be
defined systemic physiological process (VanderPloeg et al., J Environ
Pathol Toxicol Oncol 11:177-189, 1992). “In the present study, we
administered caffeine (via the drinking water, 500 mg/L) to ovariectomized,
estrogen- and progesterone-treated Balb/c mice. After 30 days of caffeine
treatment, a significant (p < 0.001) enhancement of lobulo-alveolar
development in the mammary glands of the hormone-treated mice, compared
with hormone treated control mice, was observed.”

Eur
J Epidemiol 1993 May;9(3):293-7. Unexpected effects of coffee consumption
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GB. Istituto di Medicina Clinica, Universita di Padova, Italy.
The effects of regular daily coffee consumption on liver enzymes were
studied in a large number of subjects from the general population. In
coffee drinkers, liver enzymes (gamma-glutamyl transferase, alanine-amino
transferase, and alkaline phosphatase) and serum bilirubin were lower
than in non-coffee-drinking subjects or in those consuming less than
3 cups daily. The hypothesis proposed is that liver enzymes are a target
for caffeine contained in coffee.

Anticancer
Res 1996 Jan-Feb;16(1):151-3 Suppression by coffee cherry of the
growth of spontaneous mammary tumours in
SHN mice. Nagasawa H, Yasuda M, Sakamoto S, Inatomi H Experimental
Animal Research Laboratory, Meiji University, Kanagawa, Japan.
We previously found that coffee cherry (CC), residue after removal of
coffee beans, significantly suppressed the development of spontaneous
mammary tumours of mice. In this paper, the effects of CC on the growth
of the palpable size of this type of tumour was examined. Free access
as drinking water of 0.5% solution of the hot water extract of CC
for 10 days resulted in a marked inhibition of the
tumour growth: The percent changes of
tumour sizes were 53.8 +/- 11.7% and 13.8 +/- 10.9% in the
control and the experimental groups, respectively. Associated with this,
thymidylate synthetase activity in the mammary tumours was significantly
lower in the experimental group than in the control. Normal and preneoplastic
mammary gland growth, body weight change and weights and structures
of endocrine organs were only slightly affected by the treatment. The
findings indicate that CC is promising as an antitumour agent.

Yakugaku
Zasshi 1997 Jul;117(7):448-54. [Effect of tea extracts,
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in Japanese] Shiozaki T, Sugiyama K, Nakazato K, Takeo T. “Caffeine
also showed a inhibitory effect on the
PCA reaction. These results indicate that tea could provide a significant
protection against the type-I allergic reaction. These findings also
suggest that tea catechins and caffeine play an important role in having
an inhibitory effect on the type-I allergic reaction.”

Farmakol
Toksikol 1983 Sep-Oct;46(5):107-11 [Use of the swimming test for
demonstrating antidepressive activity of drugs during single and repeated
administration]. [Article in Russian] Rusakov DIu, Val'dman AV.
“The use of the "swimming test" made it possible to identify
the activity of tricyclic (desipramine,
chlorimipramine, amitryptyline) and atypical antidepressants
(befuralin, zimelidine, trazodon), that of
pyrazidol (type A MAO inhibitor) and of a number of new compounds--derivatives
of benzofuran and morpholine upon single and chronic administration.
To define the method specificity, use was made of the neuroleptic haloperidol,
the tranquilizer diazepam, and of nembutal, which did not exhibit any
activity in the test in question.
Psychostimulants (amphetamine, caffeine) dramatically increased the
time of active swimming. The effect lasted throughout all the 30 minutes
of testing, which is not characteristic for antidepressants.”